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Prognostic Implications for Patients with Gleason Tertiary Pattern 5 Prostate Cancer

Grade 5 tertiary patterns in biopsy specimens portend worse outcomes than standard Gleason scores predict.

The Gleason scoring system is the most widely used method for grading prostate cancer tumors; it involves assessing the architectural patterns of prostate gland biopsy specimens under low-power magnification. The Gleason score is a sum of the grade (range, 1–5) for the primary pattern of the tumor (i.e., differentiation stage of most tumor cells) and the grade for the secondary pattern (i.e., differentiation stage of a minority of cells). Gleason scores range from 2 to 10, with higher Gleason scores indicating more-aggressive tumors. During the past several years, pathologists increasingly have commented on the presence of "tertiary" patterns in smaller numbers of cells. Some evidence has emerged showing that even a small proportion of tumor cells identified as undifferentiated (grade 5) can have substantial negative prognostic implications.

To evaluate the prognostic implications of tertiary pattern 5 cells, investigators in Boston evaluated 2370 men (with T1c–T3b node-negative cancer) who were treated with radical prostatectomy or radiation therapy (with or without 6 months of androgen-deprivation therapy) from 1989 through 2005. All Gleason scores were assigned by a single genitourinary pathologist. The main outcome measure was time to prostate-specific antigen (PSA) level increase (2 ng/mL higher than nadir value for radiation-therapy patients or >0.2 ng/mL with subsequent confirmatory values for surgery patients). The distribution of men by Gleason score and tertiary pattern was:

• 1059 (45%) with Gleason scores of 6
  
• 999 (42%) with Gleason scores of 7, without tertiary grade 5 patterns
  
• 36 (2%) with Gleason scores of 7, with tertiary grade 5 patterns
  
• 276 (12%) with Gleason scores of 8 to 10
  

The median follow-up was 4.2 years, and the number of recurrences was 613. The median times to PSA rise were 5.0 years for men with Gleason scores of 7 and tertiary grade 5 patterns, 5.1 years for men with Gleason scores of 8 to 10, 6.7 years for men with Gleason scores of 7 without tertiary grade 5 patterns, and 15.4 years for men with Gleason scores of 6. Men with Gleason scores of 7 and tertiary grade 5 patterns had significantly shorter times to PSA rise than did men with Gleason scores of 7 without tertiary grade 5 patterns or men with Gleason scores of 6. No significant difference was found between men with Gleason scores of 7 and tertiary grade 5 patterns and those with Gleason scores of 8 to 10.

Comment: Ironically, as we refine our ability to identify patients with higher risks at time of initial therapy, our ability to intervene with outcome-driven therapy remains nebulous. A large industry-sponsored study of adjuvant therapy after radical prostatectomy among patients with high-risk prostate cancer recently closed because of poor accrual. That event, coupled with the premature closure of a Southwest Oncology Group Intergroup study on this topic, means that definitive information regarding potential benefits of adjuvant chemotherapy or hormonal therapy likely will not be available in the near term.

— Robert Dreicer, MD, MS, FACP

Published in Journal Watch Oncology and Hematology October 2, 2007

Citation(s):

Patel AA et al. PSA failure following definitive treatment of prostate cancer having biopsy Gleason score 7 with tertiary grade 5. JAMA 2007 Oct 3; 298:1533.

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